He was a disciple of José Fernando Ramírez and Joaquín García Icazbalceta and together with them, is considered one of the most important historians of Mexico of the 19th century, ranking "as a major figure among 19th-century students of the Mexican Indian past.
From 1855 to 1857 he served as senior official of the Ministry of Development during the liberal government of Ignacio Comonfort.
In 1863 President Benito Juárez appointed him Minister of the Supreme Court of Justice of the Nation.
He returned to public life after his disgrace, and between 1880 and 1881 his masterpiece Ancient History and the Conquest of Mexico was published in four volumes.
In 1875 Orozco y Berra was a founding member of the Mexican Academy of Language, he occupied the chair XIII.